Abstract Issue/problem Individuals with chronic illnesses are at a higher risk of infections and their complications. Vaccinations are crucial in reducing this risk and their integration in chronic care pathways can enhance vaccine uptake, but it requires a collaborative approach and increased awareness in care personnel, caregivers and patients. Description of the problem The Local Health Authority of Rome 2 (ASL Roma 2, with approx. 1.3 million residents) initiated an active promotion plan for recommended vaccinations in chronic patients in January 2023, and a Clinical Vaccinology Workbook was produced to guide healthcare workers in promoting vaccinations across various care settings. The plan aims to establish collaborative agreements with hospitals and territorial structures that manage these patients, integrating vaccination plans with clinical and healthcare pathways for a more holistic approach to chronic disease management, a model that could benefit similar populations globally. Results Data was extracted from administrative databases regarding vaccinations performed in 2022 and 2023 on fragile subjects, i.e., those with a marked ‘risk condition’, aged ≥18 years. The results showed that vaccine uptake was more than doubled (6675 vs. 2041; +227%). Notably, vaccinations rose among those with oncological-hematological diseases (+212%), asplenia (+185%), chronic kidney failure or on dialysis (+190%) and those with an HIV infection (+160%). Increases were also significant in other immunocompromised conditions (+194%). Lessons The practice underlines the importance of targeted vaccination programs within chronic care management. Collaborative healthcare frameworks can significantly improve vaccination rates, reducing the burden of infectious diseases in high-risk populations. These results underscore the potential applicability of such a model in other regions and countries, highlighting the universal relevance of integrated healthcare solutions. Key messages • Collaborative, integrated frameworks between clinical and vaccination services can represent a model for increasing vaccine uptake in chronic disease patients. • Strategic partnerships and education in healthcare settings can improve vaccination rates and contribute to more holistic chronic disease management.